Young donor stem cells improve frailty in a clinical trial: What if they had their own younger cells?
Young Donor Stem Cells Improve Frailty in a Clinical Trial: What If They Had Their Own Younger Cells?
Introduction to MSC Therapy for Aging
At Forever Labs, we are passionate about leveraging autologous stem cell banking to combat aging. In my last blog post, I discussed our plan to transplant our own younger mesenchymal stem cells (MSCs) to our older selves for the purposes of rejuvenation. Interestingly, a clinical trial was recently concluded where young donor (allogeneic) MSCs were transplanted into elderly individuals to treat age-related frailty [1].
Clinical Trial Results
This study found that a single dose of 100M young allogeneic MSCs provided benefit in older people. Specifically, aged individuals treated with 100M young allogeneic MSCs showed improvement on a 6-minute walk test, a short physical performance exam, and had improved forced expiratory volume. Also, some proteins associated with inflammation were reduced.
These are encouraging results.
Limitations of Allogeneic MSCs
That said, some data from this trial suggests that the use of allogeneic MSCs limited the effectiveness of this treatment.
Dr. Benjamin Buller previously wrote a post on why your own cells matter. In short, allogeneic MSCs do not remain in your body long, and as foreign cells, they have the potential to elicit an adverse immune response. For this reason, allogeneic MSCs are a double-edged sword: they can provide short term benefit intrinsic to MSCs, but they are removed by your immune system in a manner than may have negative effects [2, 3]. This clinical trial had three treatment groups: 1) Placebo, 2) 100M allogeneic MSCs, and 3) 200M allogeneic MSCs. The cells were administered in a single intravenous injection. Of interest, whereas the 100M cell dose resulted in physical improvement in patients, the higher 200M cell dose did not.
Exploring the Dose Discrepancy
Why would this be?
One possibility is that 200M MSCs is simply too many cells, however, it is within a dose range that is commonly given in MSC therapies. Another possibility is that 200M allogeneic MSCs results in negative effects due to immune rejection.
In this trial, one patient treated with 100M cells had a mild increase in donor-specific antibodies, whereas two patients treated with 200M cells had a moderate increase in donor-specific antibodies. In addition, two other patients treated with 200M cells had a moderate increase in ‘panel reactive antibodies’ (PRA) that were not considered to be donor specific. A high PRA indicates that someone has been exposed to ‘non-self’ proteins and that they have developed antibodies against them. This data suggests a possibility of immune sensitization, but it is not conclusive.
Balancing Immune Responses
That said, MSCs are often used for their ability to reduce inflammation by immune-suppression. In this trial, patients that received either 100M MSCs or 200M MSCs had a reduction in some inflammation associated proteins (TNF-α), and the presence of some immune cell markers (CD8 and CD25), whereas placebo did not, which suggests some general and beneficial immunomodulation from the donor cells. What this means, is that allogeneic MSCs may be both stimulating an immune response, because they are foreign, but also suppressing an immune response, because that is what MSCs do. It is difficult to say why the 200M allogeneic MSC dose did not provide physical benefit, but given that 40% of patients in the 200M cell dose had a detected antibody response, it should be considered.
Challenges of Immune Sensitization
It is also worth mentioning that one problem with immune sensitization, is that it prevents further use of the same cells. Once you have developed anti-bodies to a specific donor, your immune system will efficiently attack tissue from that donor. Thus, using the same donor cells more than once becomes less effective, if not risky. As with most things biological (and all things immunological), interpretation is complicated. As mentioned, this study is a very small one. Therefore, it is difficult to draw firm conclusions.
The Promise of Autologous MSCs with Forever Labs
It is very promising to find that MSCs have the potential to treat symptoms of aging in humans. However, the higher dose of young donor MSCs did not provide physical benefit whereas a lower dose did. As some higher dose patients displayed an immune response against them, the use of donor cells is likely limited by immune rejection.
It would be interesting to see the effects if patients were treated with their own young MSCs. We are going to find out.
Why This Matters for Forever Labs
At Forever Labs, we focus on banking your own bone marrow-derived MSCs through a minimally invasive, FDA-compliant procedure at foreverlabs.com. Unlike allogeneic MSCs, autologous cells avoid immune rejection, offering a safer, more effective option for future therapies. By banking your MSCs in your 20s or 30s, when they are at peak potency, you ensure they are available for personalized treatments to address age-related frailty, as explored in this study. Our cryogenic storage keeps your cells viable for decades, aligning with the growing evidence of MSC potential in regenerative medicine.
Take Charge of Your Aging Journey
The Journal of Gerontology study shows that MSCs can improve frailty, but donor cells face immune challenges. At Forever Labs, we’re committed to unlocking the full potential of your own MSCs. Visit foreverlabs.com to learn how stem cell banking can prepare you for future rejuvenation therapies. Age on your terms with Forever Labs.
Tompkins BA, et al. Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial. J Gerontol A Biol Sci Med Sci. 2017, 72(11):1513-1522.
Ankrum JA, et al. Mesenchymal stem cells: immune evasive, not immune privileged. Nat Biotechnol. 2014, 32(3): 252–260.
Oliveira RL, et al., In Vivo Immunogenic Response to Allogeneic Mesenchymal Stem Cells and the Role of Preactivated Mesenchymal Stem Cells Cotransplanted with Allogeneic Islets. Stem Cells Int. 2017, 9824698.